Discovery of Alternative Producers of the Enediyne Antitumor Antibiotic C-1027 with High Titers

Xiaohui Yan, Hindra, Huiming Ge, Dong Yang, Tingting Huang, Ivana Crnovcic, Chin-Yuan Chang, Shi Ming Fang, Thibault Annaval, Xiangcheng Zhu, Yong Huang, Li Xing Zhao, Yi Jiang, Yanwen Duan, Ben Shen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The potent cytotoxicity and unique mode of action make the enediyne antitumor antibiotic C-1027 an exquisite drug candidate for anticancer chemotherapy. However, clinical development of C-1027 has been hampered by its low titer from the original producer Streptomyces globisporus C-1027. Here we report three new C-1027 alternative producers, Streptomyces sp. CB00657, CB02329, and CB03608, from The Scripps Research Institute actinomycetes strain collection. Together with the previously disclosed Streptomyces sp. CB02366 strain, four C-1027 alternative producers with C-1027 titers of up to 11-fold higher than the original producer have been discovered. The five C-1027 producers, isolated from distant geographic locations, are distinct Streptomyces strains based on morphology and taxonomy. Pulsed-field gel electrophoresis and Southern analysis of the five C-1027 producers reveal that their C-1027 biosynthetic gene clusters (BGCs) are all located on giant plasmids of varying sizes. The high nucleotide sequence similarity among the five C-1027 BGCs implies that they most likely have evolved from a common ancestor.

Original languageEnglish
Pages (from-to)594-599
Number of pages6
JournalJournal of Natural Products
Volume81
Issue number3
DOIs
StatePublished - 23 Mar 2018

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